Influence of the Basal Ganglia on Cerebellar Action

描述（由申请人提供）：

DESCRIPTION (provided by applicant): Advances in imaging and micro-electronics now enable neurosurgeons to identify small regions of the brain and implant electrodes to activate cells in those regions. Deep brain stimulation (DBS) is proving to be a surprisingly effective approach for the control of movement disorders associated with diseases of the basal ganglia, such as Parkinson's disease. In Parkinson's patients, DBS can eliminate or reduce tremor, akinesia and drug-induced dyskinesias. These motor disorders are often totally disabling in advanced stages of the disease. Recent multi-group studies have demonstrated that DBS can provide effective symptomatic relief to Parkinson patients for periods extending over several years. However, the use of DBS is in its infancy, and no one knows the appropriate brain regions to stimulate to achieve optimal behavioral improvement. The goal of our research is to understand how the nervous system controls limb movements. We are particularly interested in characterizing regions of the brain that control the limb during reaching to grasp an object. Parkinson's patients experience difficulty in initiating and performing the reach-to-grasp, but the movement can be improved by stimulating or destroying specific regions of the basal ganglia. We believe that output from the basal ganglia interferes with normal operation of brainstem motor nuclei that receive input from the cerebellum. Our research has identified several brainstem regions of the cat that integrate basal ganglia and cerebellar output. Our colleagues have applied these findings to guide DBS in the human and have produced effective relief of motor symptoms related to Parkinson's disease and multiple sclerosis. The proposed studies will use cats as subjects to: 1) Identify and characterize cells in the basal ganglia output nuclei that discharge during reaching to grasp. 2) Determine the importance of these cells for reaching and grasping by temporarily inactivating or stimulating them with chemical substances and recording effects on movement. 3) Develop a unilateral model of Parkinson's disease by destroying dopaminergic cells with injections of 6-OHDA. 4) Attempt to normalize limb movements in the 6-OHDA model by inactivating or activating specific regions of the brainstem. The data will help us understand how DBS works and will identify candidate regions for the use of DBS in the treatment of motor disorders.